AIDS (acquired immune deficiency syndrome) has assumed the status of a major health threat. HIV1 (the predominant form of the human immunodeficiency virus) currently infects at least a million people in the USA and millions more abroad. Substantial research efforts are now being directed toward the development of a vaccine against this fatal disease. The long-term objective of the proposed research is to simulate the three-dimensional structures of molecules which are likely to be AIDS vaccine candidates. Such theoretical studies may provide insight into immunological properties of these molecules which would have a bearing on vaccine design. Specific aims include the development of models for segments of GP160 (160 kilodalton glycoprotein), the initial product of an HIV1 gene, which is cleaved to form envelope proteins GP120 and GP41. These products coat the virus and are important in binding and invading T4 lymphocytes of the human host. Thus, these proteins or peptides derived from them may show particular promise as vaccine candidates which would stimulate a protective immune response. The proposed methodology employs an approach which produced promising results when applied to a malarial peptide vaccine candidate. Published amino acid sequences and models based on conformational preference parameter predictions of secondary structure will be used as a starting point. Searches for homology between GP160 and proteins with structures known by X-ray crystallography will be performed. In addition, regions predicted to have a high probability of ordered secondary structure from Robson information content theory will be identified. Among these, peptides known or expected to have immunological significance will be selected for analysis. Computer models of promising peptides folded into reasonable three-dimensional shapes will be produced. These will be used as trial structures for conformational exploration involving energy minimization and molecular dynamics simulations using molecular mechanics software developed in the laboratory of M. Karplus. Experimental work now in progress by other groups may provide X-ray crystallographic structures or proton-proton distances from nuclear magnetic resonance studies of nuclear Overhauser effects, which would greatly assist refinement of the models.